A Novel Hybrid Silk Fibroin/Polyurethane Arteriovenous Graft for Hemodialysis: Proof‐of‐principle Animal Study in an Ovine Model

BACKGROUND In an attempt at answering the need for a valuable and durable hemodialysis vascular access, a novel semi‐degradable hybrid vascular graft, manufactured by electrospinning using silk fibroin and polyurethane (Silkothane®), has been developed and characterized in vitro according to standards. OBJECTIVES In this proof‐of‐principle animal study, we aimed at evaluating the performances of Silkothane® grafts in a sheep model of arteriovenous shunt, with respect to patency and short‐term graft remodeling. MATERIALS AND METHODS Nine Silkothane® grafts (6mm inner diameter, ≈7cm long, ≈400μm thick) were surgically placed into the left cervical fossa of nine female sheep, between the common carotid artery and the external jugular vein. During the housing period the animals were treated with an inhibitor of platelets aggregation. Grafts were examined by palpation three times per week, and by duplex ultrasound every two weeks to exclude significant stenosis, dilation, presence of thromboses, neointimal proliferation or other complicating features. The sheep were euthanized at 30, 60 and 90 days (N=3 for each group). At sacrifice, grafts were harvested, fixed, and submitted for histologic, immunohistochemical and Scanning Electron Microscopy examination. RESULTS No cases of graft‐related complications (e.g. seroma formation, transgraft bleeding, aneurismal dilation, calcification, structural yielding) were recorded in this study. One graft failed due to a thrombotic event likely related to a technical error (11%). One sheep had post‐operative wound infection, surgically resolved (11%). Four out of nine sheep (44%) showed post‐operative edema, usually disappearing in 7 days. Eight of nine sheep (89%) showed 100% primary unassisted patency at the respective time of sacrifice, as confirmed by palpation and ultrasound evaluation (average flow rate 1.76 ± 0.61 l/min). Histological, immunoistochemical and SEM analysis evidenced signs of inflammation and formation of neointimal hyperplasia at the venous anastomosis, as it typically happens with arteriovenous fistulae and synthetic grafts. CONCLUSIONS In our ovine model of arteriovenous shunt, Silkothane® grafts provided evidences of safety and efficacy in granting 100% patency up to 90 days. Further studied need to be conducted in order to directly compare the novel grafts with commercially available synthetic grafts.